Systems and methods for measuring fluid properties

ABSTRACT

A fluid property measurement system for measuring free stream particulates includes a fluid movement device positioned within a fluid container which is configured to cause fluid flow within the fluid container along a fluid flow path when a fluid is present. A constricted region along the fluid flow path generates a region of concentrated streamlined flow within the constricted region and mixing of the fluid outside of the constricted region. A property measuring device is positioned with respect to the constricted region to measure fluid properties in the region of streamlined flow.

RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.11/504,970, filed Aug. 15, 2006, and now U.S. Pat. No. 7,393,690, issuedJul. 1, 2008, which is a continuation-in-part of U.S. patent applicationSer. No. 10/431,358, filed on May 6, 2003, and now U.S. Pat. No.7,262,059, issued Aug. 28, 2007, each of which is hereby incorporatedherein by reference in its entirety.

FIELD OF THE INVENTION

The present invention relates generally to methods for measuring fluidproperties, such as fluid suspension properties. More particularly, inone embodiment, the present invention relates to measuring bloodplatelet function.

BACKGROUND OF THE INVENTION

Currently, there are over 2 million hospitalizations and nearly 10million visits to physicians that are associated with coronary heartdisease in the United States every year. A majority of these patientsreceive some form of antiplatelet therapy, e.g. Aspirin, Plavix, etc.,to prevent acute thrombosis and clotting associated with vascularinterventions, such as angioplasty, or implants, such as coronarystents. Excess dosage of the antiplatelet drugs can result in bleedingcomplications because the platelet function is over-suppressed, whileinsufficient dosage can fail to prevent acute thrombosis and clottingdue to insufficient suppression of platelet function. Thus, it would bevaluable to assess platelet function in patients at certain points ofcare and adjust the antiplatelet drug dosage to the specific needs ofeach individual. The relevance of such a point-of-care approach isbecoming increasingly important in the context of platelet GP IIb/IIIaantagonists, e.g. Abciximab, Tirofiban, Eptifibatide, etc., with shorthalf-lives (typically about 1 hour) that can be adjusted carefully andquickly to meet the needs of each patient. Thus, an effectivepoint-of-care platelet function assay that enables management oftherapeutic regimen has considerable clinical value.

A platelet aggregometer is an instrument that can assess certain aspectsof platelet function. This device can be used by starting with aplatelet suspension, such as blood or platelet rich plasma, which can becollected from a patient and dispensed into a disposable sample holderof the platelet aggregometer. A chemical stimulus, such as collagen, canbe added to the platelet suspension in the sample holder, and subsequentagitation/mixing of the platelet suspension with the stimulus can causethe platelets to aggregate. The characteristics of this aggregation canbe measured by various methods known by those skilled in the art, andthe degree of aggregation measured can be directly related to thefunction of the platelets.

Currently available methods in the field of platelet aggregometersinclude sample holders that provide thorough mixing and agitation of theplatelet suspension to cause platelet aggregation. However, most ofthese methods and devices create flow that is not conducive to enablingcertain detection modalities of platelet aggregation, particularly forlight scattering methods.

Many methods utilize mechanical mixing which often damages or otherwisealters fluid characteristics. For example, the use of a roller pump hasbeen one proposed method for moving blood. However, the compression of aflow conduit containing blood by means of rollers often disfiguresplatelet aggregates, damages red cells, and alter their characteristics.Thus, the ergonomics of such designs can be undesirable, and loading ofthe blood sample and/or the chemical stimulus that causes plateletaggregation can be cumbersome. These limitations detrimentally influencethe quality and consistency of platelet aggregation, which in turnadversely affects the reproducibility and reliability of the measurementof platelet function. Other methods include designs that presentrelatively good flow patterns for measurement using light scatteringtechniques, but do not provide significant mixing that induces morethorough and consistent platelet aggregation.

SUMMARY OF THE INVENTION

It has been recognized that there is a need to develop systems andmethods that provide good mixing properties, without substantial damageto blood aggregates or other fluid properties to be measured. At thesame time, such a system can also provide streamlined flow in a distinctregion for accurate measurement of a fluid property. The presentinvention addresses the limitations of previous methods and presentsfluid measurement devices and methods that enable more reliableassessment of platelet function, or in the case of other fluids, morereliable assessment of a desired fluid property.

In a first embodiment, a fluid property measurement system for measuringfree stream particulates can include a fluid movement device positionedwithin a fluid container to cause fluid flow within the fluid containeralong a fluid flow path. The fluid movement device can often be a rotoralthough other devices can also be suitable. The system can furtherinclude a constricted region along the fluid flow path which generates aregion of concentrated streamlined flow within the constricted regionand mixing of the fluid outside of the constricted region. A propertymeasuring device can also be functionally positioned with respect to theconstricted region to measure fluid properties in the region ofstreamlined flow. In one detailed aspect of the present invention, theconstricted region can be formed by a stenotic baffle system. Theconstricted region and fluid movement device can advantageously beconfigured to provide free stream aggregation of material such thatmeasurement of aggregation can be based on free stream properties.

In another embodiment of the present invention, a method for measuringfree stream properties of a fluid can include placing a quantity offluid in a container and inducing flow in the fluid. The induced flowcan be substantially streamlined in at least a measuring region of thecontainer by constricting flow. Further, the fluid can be recirculatedthrough the measuring region. A mixing region can be created separatefrom the measuring region sufficient to substantially mix the fluid anda property of the fluid can be measured in the measuring region. Thesystems and methods of the present invention provide an improvedaggregation measurement of biological fluids while also minimizingadverse affects on the fluid properties such as platelet function.

Additional features and advantages of the invention will be apparentfrom the detailed description which follows, taken in conjunction withthe accompanying drawings, which together illustrate, by way of example,features of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1A is a perspective view of a fluid measurement device inaccordance with an embodiment of the present invention.

FIG. 1B is a perspective view of a fluid measurement device inaccordance with another embodiment of the present invention showingalternative rotor and disruption members.

FIGS. 2A, 2B, and 2C are perspective views of various rotors inaccordance with embodiments of the present invention, shown within across-sectional view of side walls of a fluid container.

FIG. 3 is a perspective view of several representative disruptionmembers for use in accordance with embodiments of the present invention.

FIGS. 4A and 4B illustrate cross-sectional views in accordance with aforced flow embodiment of the present invention.

FIG. 5A is a cross-sectional view of a fluid property measurement systemhaving a stenotic baffle system in accordance with an embodiment of thepresent invention.

FIG. 5B is a cross-sectional view of the embodiment shown in FIG. 5Ahaving the rotor removed.

FIG. 5C is a top view of the embodiment shown in FIG. 5A having the capremoved.

The drawings are intended to illustrate several specific embodiments ofthe present invention and are not intended to be unnecessarily limiting.As such, departure may be had in dimensions, materials, and featureswhile still falling within the scope of the invention.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S)

Reference will now be made to the exemplary embodiments illustrated inthe drawings, and specific language will be used herein to describe thesame. It will nevertheless be understood that no limitation of the scopeof the invention is thereby intended. Alterations and furthermodifications of the inventive features illustrated herein, andadditional applications of the principles of the inventions asillustrated herein, which would occur to one skilled in the relevant artand having possession of this disclosure, are to be considered withinthe scope of the invention.

In describing and claiming the present invention, the followingterminology will be used.

The singular forms “a,” “an,” and “the” include plural referents unlessthe context clearly dictates otherwise. Thus, for example, reference to“a rotor” includes reference to one or more of such structures, andreference to “a stimulus” includes reference to one or more of suchfactors.

As used herein, “recirculating,” “recirculated,” or “recirculation”refers to fluid flow along a path that is primarily related to ameasuring region where fluid recirculation occurs, though recirculationcan also occur in other non-measuring regions. By recirculating in themeasuring region, a better measurement sample over a predetermined timecan be taken as to the properties of the fluid. For example, in oneembodiment, recirculation can occur by circumferential recirculation,and in another embodiment, the recirculation can be by bi-directionalrecirculation.

As used herein, “fluid” refers to a flowable composition and can includeliquid, gas, suspended solid or other flowable mass. Fluids can be inthe form of suspensions, emulsions, solutions, mixtures, or the like.

As used herein, “mixing” refers to disturbed flow or separated flow of afluid. In one embodiment, the addition of a chemical stimulus can beaccompanied by mixing in order to facilitate distribution of thestimulus sufficient to affect the bulk properties of the fluid. As usedherein, mixing does not include mixing that is merely the result ofintermolecular, intercellular, or structural forces exerted within afluid under substantially streamlined flow, or which is solely theresult of diffusion due to concentration gradients.

As used herein, “streamlined” refers to a fluid flow state that is morestreamlined than is present in a mixing region acting on the same fluid.Additionally, a streamlined flow is capable of providing fluid flowdynamics such that at least a substantially accurate measurement can betaken, such as by use of a light scattering device or other fluidproperty measuring device. Further, streamlined flow typically refers tominimally disturbed flow that can be predominantly laminar, includingarcuate flow in case of a cylindrical container. Such flow is suitablefor testing using methods such as light scattering, etc. Although acommon definition of the term “streamlined” can define a path or pathscharacterized by a moving particle in a fluid such that the tangent tothe path at every point is in the direction of the velocity flow, theterm as used herein is intended to be broader in scope to include flowthat is minimally disturbed such that more accurate readings using fluidmeasuring equipment can be used, e.g., light scattering particledetection devices.

As used herein, “free stream particulates” refers to masses which arenon-liquid materials contained within a fluid which are not attached toa fixed structure such as a container wall or other solid member. Freestream particulates can include, but are not limited to, plateletaggregates, solid debris, air bubbles, clots, and the like.

As used herein, “stenotic” refers to any constriction or narrowing of afluid flow path. Typically, stenotic baffles can have a graduallynarrowing portion which leads to a flow path portion havingsubstantially constant cross-sectional area, and a subsequent expandingportion where cross-sectional area gradually increases to anunobstructed flow.

As used herein, the term “concentrated” when referring to streamlinedflow, indicates that a greater number of streamlines per unit area arepresent than are present in other areas of the system in accordance withembodiments of the present invention. Areas outside of where there is“concentrated” streamline flow can be from streamlined (though lessconcentrated) to chaotic.

As used herein “fluid dynamic focus,” “fluid dynamically focused,” orthe like, refers to fluid conditions where elements of the fluid are canbecome concentrated in a smaller cross-sectional area of controlledvolume of flow.

Concentrations, amounts, and other numerical data can be presentedherein in a range format. It is to be understood that such range formatis used merely for convenience and brevity and should be interpretedflexibly to include not only the numerical values explicitly recited asthe limits of the range, but also to include all the individualnumerical values or sub-ranges encompassed within that range as if eachnumerical value and sub-range is explicitly recited. Further, such aninterpretation should apply regardless of the breadth of the range orthe characteristic being described.

As illustrated in FIG. 1A, a system, indicated generally at 10 a, inaccordance with embodiments of the present invention, is shown formeasuring a property of a fluid. A variety of fluids can be suitable formeasurement using the method of the present invention. Suitable fluidsinclude, but are not limited to, physiological fluids such as plateletsuspensions, platelet rich plasma, whole blood, leukocyte suspensions,erythrocyte suspensions, plasma, red blood cell suspensions, urine,bile, etc. Additionally, physiologically compatible fluids, such assaline, or immiscible fluids, such as oils (with water based fluids) canbe added to a fluid to be measured for a desired purpose. In oneembodiment, these or other fluids can contain exogenous additives suchas polymer microbeads, cells, powders, or combinations thereof. Theseadditives can facilitate measurement or otherwise affect the fluid so asto improve handling and/or measurement. Other non-physiological fluidssuch as coal and other slurries can also be contained and assessed usingthe sample holder described herein. The following description andexamples are described using a platelet suspension or other bloodcomponent-containing fluid, such as whole blood. This has been done forconvenience, and is only an example of one of the types of fluid thatcan be used with the present invention.

In accordance with one aspect of the present invention, a fluidcontainer 12 is configured for recirculating fluid. The fluid containercan be shaped so as to allow fluid to circulate within the containerrecursively. The fluid flows unidirectionally in a substantiallycircular pattern in FIGS. 1A, 1B, and 5A-C, however any recirculatingflow can be used in accordance with embodiments of the presentinvention, such as bi-directional recirculating flow as is described inFIGS. 4A and 4B, discussed below. In one aspect of the invention, thefluid container can provide for an essentially batch process whereinfluid is introduced into the container either in a single charge orincrementally. In either embodiment, the flow of the fluid inside thecontainer generally follows a recirculating path through the same regionor regions.

Returning to discussion of FIG. 1A, in accordance with one aspect of thepresent invention, the fluid container 12 can be comprised of anymaterial that is compatible with a chosen fluid to be mixed and aproperty measured. Additionally, the fluid container 12 can beconfigured to facilitate measurement of various properties using knownmethods. For example, if the fluid container were intended for use witha light scattering whole blood platelet aggregometer (LSWBPA), thecontainer that holds the fluid can be made of transparent or translucentmaterials that permit passage of light through the container walls andinto the fluid. Many plastics such as, but not limited to,polycarbonates, polyacrylates, polystyrenes, polyvinylchlorides,polyurethanes, and other polymeric materials, fulfill these criteria.Glass can also be acceptable depending on the fluid and duration ofexposure to the fluid. Typically, when the fluid is a bloodcomponent-containing fluid, the fluid container can be formed of arelatively small size that is capable of handling very small volumes offluid. In one aspect of the present invention, the fluid container has avolume of less than 10 ml, while an internal volume of less than about 2ml is sufficient. One current embodiment of the present invention has aninternal fluid capacity from about 0.05 ml to 0.5 ml. Generally, thefluid containers can have a volume from about 0.02 ml to about 30 ml.

In another aspect of the present invention, a measuring region orstreamlined flow region 28 is provided distinct from a mixing region 26.The measuring region 28 is configured for providing substantiallystreamlined flow of the fluid within the fluid container 12. Flow offluid within the container 12 can be induced by a method that isnon-destructive of the fluid or its properties. Such methods include theuse of a rotor 20 a, other mixer (not shown), stir bar (not shown),forced flow device (not shown), or an external drive (not shown). Theseand other means for inducing flow can also be suitable for use in thepresent invention, but should provide a streamlined region 28, andshould not adversely affect the fluid properties. Preferred methods forinducing flow in a blood component-containing fluid will not damageaggregates, destroy coagulated masses, or otherwise adversely affect theblood components, such as by causing significant hemolysis.

In this embodiment, the rotor 20 a is a cylindrical body having aconical portion at a bottom end. The rotor can be rotated and securedusing shaft 22 a and cavity 22 b system. The shaft 22 a can be coupledto a constant or variable speed motor 24 that can be used to adjust therotational speed based on the fluid properties, such as viscosity orfragility. Depending on the viscosity of the fluid, the rotor speed canvary from one medium to another, while the rotor 20 a is being driven bynon-varying force. In some scenarios, it may be desirable to maintainthe rotor speed at a particular value. This can be accomplished byeither using a large driving force to drive the rotor 20 a, or byproviding a motor 24 equipped with a feedback control to either increaseor decrease the rotor driving force by means of monitoring the rotorspeed. This embodiment generates general circumferential recirculationof the fluid within the system.

As mentioned, the fluid container 12 includes a mixing region 26configured for substantial mixing of the fluid in the fluid container.The mixing region 26 is a region within the container 12 in which thefluid is mixed, and which is separate from a measuring or streamlinedflow region 28. The mixing that can occur in the mixing region 26 can beturbulent or more gentle in action, but should be sufficient tosubstantially mix or homogenize the composition of the entire fluid.Thus, the measurement of fluid properties in the separate measuringregion 28 can be representative of the bulk properties of the fluid. Theseparation of mixing region 26 and measuring region 28 allows forincreased control of the fluid flow environment, and improves theability to prevent damage to the fluid. The mixing region 26 can beproduced using a variety of disruption members 14 a, 14 b, and/or 14 c,such as a stationary obstruction, movable obstruction, rotating mixer,vagile object, or combinations thereof. These disruption members cancause a local disruption or turbulence in the streamline flow of thefluid sufficient to mix the fluid.

In one aspect of the present invention, the disruption members 14 a, 14b, 14 c protrude from an inside surface 16 of the fluid container 12.The disruption members 14 a, 14 b, 14 c can be molded as an integralpart of the container, or can be separately formed members.Additionally, the disruption members 14 a, 14 b, 14 c can be attached tothe inner surface 16 in a permanent or removable manner. FIG. 1A showsdisruption members 14 a and 14 c as stationary obstructions affixed tothe inner surface 16 side walls of the fluid container 12. Disruptionmember 14 c is also shown wherein baffles are affixed to an elongatedrod member 18. The rod member 18 can be a rotating or fixed shaft, or ahollow tube inlet for introducing fluid or other material into the fluidcontainer. Disruption member 14 b is a stationary obstruction affixed tothe inner surface 16 bottom of the fluid container 12.

One or more disruption member 14 a, 14 b, 14 c can affect mixing in themixing region 26 in the vicinity of the one or more member 14 a, 14 b,14 c. Three different disrupting members are shown for exemplarypurposes only. One disrupting member is typically sufficient to providedisturbed flow, or even turbulent flow, though more than one can bepresent at or near the mixing region 26 in some embodiments.

The mixing region 26 can vary in size depending on such variables as thefluid flow velocity approaching the disruption members, fluid viscosity,and the particular shape of the disruption member(s). Often a singledisruption member and mixing region is sufficient to produce substantialmixing of the fluid. However, as shown in FIG. 1A, multiple mixingregions can be present.

In one embodiment, the surfaces that contact the fluid, i.e., rotor 20 aand/or inside surface 16, can be configured to be highly compatible withthe introduced fluid, and can also be configured to avoid contaminationof the fluid and/or deterioration of the surfaces. For example, thefluid container 12, if made for use with platelet suspensions, can bemade of materials that are generally compatible with the plateletsuspension. Additionally, it may be desirable for aggregates not toadhere to surfaces within the apparatus or system 10 a, such as theinner surface 16 of the fluid container 12, the rotor 20 a, thedisruption member(s) 14 a, 14 b, 14 c, or other parts of the apparatus.This can be accomplished by using smooth geometries in the apparatusand/or coatings, such as lubricious, hydrophilic, or hydrophobiccoatings on the apparatus components. Such coatings, if used, canincrease biocompatibility and/or decrease friction and associatedadherence to the coated surfaces. Coatings suitable for use in thepresent invention can include, but are not limited to, hydrophilic,hydrophobic, lubricious, heparin, carbon-diamond, or ceramic coatings.

In addition to the above components, the fluid container 12 can have acap 34 to hold the fluid within the fluid container 12 and preventspillage of the contents. The cap 34 can be made of a material that hassimilar properties to that of the fluid container 12, e.g. sufficientmechanical strength and compatibility with the fluid. The cap 34 canalso be formed as an integral part of the fluid container 12.Optionally, the cap can also contain self-sealing ports through whichthe fluid and/or additional material, such as stimuli, can beintroduced. In one embodiment, fluid can be introduced through an inletline 36, or through depositing the fluid into the fluid container 12prior to securing the cap 34. The inlet line 36 can be configured asshown in FIG. 1A, or can be an aperture (not shown) in the wall of thefluid container. Optionally, the inlet can be in an opening on adisruption member, as shown in with respect to disruption member 14 c(inlet line 18). In an alternative embodiment, a volume of fluid inexcess of what is desired can be dispensed into the container, such thatwhen the cap 34 is placed on the fluid container 12, a portion of themedium overflows out of the container 12 to achieve the desired volumeof medium inside the container 12. Alternatively, the fluid container 12can be pre-evacuated for a specific volume so that the plateletsuspension or other fluid can be drawn into the container 12 by vacuumfor the desired volume.

In another aspect of the present invention, a property measuring device32 can be operatively associated with the measuring region. The propertymeasuring device 32 can be a light scattering whole blood plateletaggregometer (LSWBPA), or another known light scattering device, opticaldevice, ultrasound, electro-magnetic device, or mechanical device.

The above-described device can be used to measure a variety of fluidproperties such as, but not limited to, platelet and leukocyteaggregation, degree of coagulation, particle count, density, viscosity,temperature, hematocrit, chemical composition, fluorescence, refractiveindex, absorption, attenuation, elasticity, compressibility, dielectricstrength, impedance, echogenecity, specific heat, heat conductivity,osmolarity, diffusivity, and/or pH. A currently recognized use of thepresent invention is in the measurement of platelet aggregation of bloodcomponent-containing fluids. In this embodiment, the bloodcomponent-containing fluid can be introduced into the fluid container 12through inlet 36 (or inlet 18). A stimulus, such as an aggregatingagent, can be introduced into the blood component-containing fluid,which can cause a change in the blood component-containing fluidproperties. The desired fluid properties can be measured and recordedusing the property measuring device 32, which is typically operativelyassociated with the measuring region 28 of the fluid. Additionally, abaseline measurement of the property of interest can be taken prior toor shortly after introduction of the stimulus in order to quantify theeffect of the stimulus on the fluid. The fluid container 12 with itscontents can then be disposed of or recycled for future use.

FIG. 1B depicts an alternative embodiment, illustrated generally at 10b, wherein a series of baffles 14 d are used to provide separated flowin the mixing region 26. Additionally, the rotor 20 b has a flat top andcan be controlled by a motor 24 that is positioned below the container12. Alternately, the rotor 20 b can be controlled by a rotating magnetpositioned above or below (not shown). An alternative cap 34 is shownhaving two inlets 36 and no shaft aperature, though more or less inletscan be present. Again, a light scattering device 32 is shown inoperative communication with a measuring or streamlined flow region 28.Embodiments of the present invention utilizing this or otherrotor-induced motion devices in the fluid can create low shear stressesinto the fluid. At appropriate rotation speeds, this or other similarconfiguration can provide mixing and streamlined flow without causingsignificant damage to the fluid and particulates, such as plateletaggregates, and does not detrimentally alter the properties of thefluid.

Regarding the above and other embodiments, with respect to the stimulusthat can be used, the stimulating agent that is introduced into thefluid to elicit response can be mechanical, electromagnetic, biological,chemical, or other stimulus. For example, in a platelet suspension, theplatelets in the fluid container can be subjected to certain fluiddynamic forces in order to activate them via mechanical stimulus.Alternatively, the fluid can be subjected to electromagnetic stimulususing an electromagnetic field to elicit a response. In yet anotheralternative embodiment, the fluid can be subjected to biological agentssuch as bacteria, viruses, other platelets or white cells, or similaragents that cause a measurable biological response in the fluid. Theresponse to the stimulus is usually the aggregation, agglutination,coagulation, or other types of clumping of the platelets within thefluid. Although introduction of a single stimulus is usually sufficient,several stimuli can also be introduced either simultaneously orsequentially. A pre-stimulus baseline measurement of the plateletsuspension can be established while flow is induced in the fluid insidethe container at an initial time prior to introducing the stimulus.

Specific stimuli that can be used for specific types of fluid areincluded by way of example, as follows. If a platelet-containing fluidis being used to measure platelet function, variousactivating/aggregating agents can be used alone or in combination,including adenosine di-phosphate (ADP), collagen, thrombin, epinephrine,ristocetin, calcium ionophore, thrombin receptor agonist protein (TRAP),arachidonic acid, and combinations thereof. If leukocyte function is tobe measured, to a leukocyte-containing fluid can be added effectiveamounts of a leukocyte aggregating agent. Such leukocyte aggregatingagents can include calcium ionophore, formyl-methyl-l-phenylalanine, orcombinations thereof. Plasma or blood activating agents can includethrombin, diatomaceous earth, kaolin, celite, glass particulates,trypsin, pepane, phospholipids, or combinations thereof.

In keeping with the present invention, there are several mechanisms bywhich the stimulus can be introduced into the fluid. Chemical and/orbiological stimuli can be injected into the fluid by a pipette, aneedle, or other types of injection devices. Alternatively, the stimuluscan be pre-dispensed onto an interior surface (e.g. by coating) withinthe container such as a disruption member, baffle, rotor, or innersurface of the container. In keeping with the present invention, thestimulus can also be dispensed into the fluid container prior to theintroduction of the fluid into the container, in which case, a baselinecan be quickly established before the onset of the response. In yetanother optional embodiment, the stimulus can be introduced into thefluid after placing the fluid into the container.

The fluid response can be measured as the fluid components react to thestimulus. Such a response can be a change in viscosity, luminescence,conductivity, or other properties of the fluid. For example, withplatelet containing fluids, the measured response is the number of theplatelet aggregates of a minimum size as they form and disintegrate. Thesize of these platelet aggregates can also be measured as another typeof response. Other combinations of number and size can also be measured.Further, an overall change in scattered light can be measured to reflecta change in bulk properties. These responses are recorded andsubsequently analyzed so as to assess the functions of the plateletunder investigation. At the conclusion of the test the fluid and thefluid container can be discarded. Alternatively, parts of the apparatuscan be salvaged and recycled. The process of the present invention canalso be considered essentially a batch process or closed system for theperiod between introduction of the stimulus and the final measurement ofthe target property.

Turning now to FIGS. 2A, 2B, and 2C, various alternative rotorconfigurations are shown, though other configurations can also besuitable for use. FIG. 2A shows a rotor 20 c which includes two diskshaped members connected by a shaft. The fluid to be mixed and measuredcan be present between the two disks. A disturbing member (not shown)can be between the two disks of the rotor 20 c, providing separated flowin a mixing region. The rotor 20 c may or may not leave sufficient spacebetween the disk edges and the inner surface 16 of the fluid container12 to allow fluid to flow therethrough.

FIG. 2B shows another alternative rotor 20 d that includes a single diskconnected to a shaft. The rotor 20 d may or may not leave sufficientspace between the disk edges and the inner surface 16 of the fluidcontainer 12 to allow fluid to flow therethrough.

FIG. 2C shows yet another alternative rotor 20 e including a generallycylindrical member having a conical shape at each end. The length of therotor 20 e can correspond roughly to the height of the fluid container12, such that the points 21 of the rotor 20 e correspond to and couplewith associated cavities or other retaining members (not shown) on theinner surface 16 of the fluid container 12 or cap (not shown). Rotor 20e can include a magnetically responsive element formed inside the rotorso as to enable rotation based on a magnetic field similar to theoperation of a magnetic stir bar. Typically, a rotor having acylindrical or conical shape provides good flow results and isrelatively simple to manufacture.

Other suitable shapes for use in the rotor aspect of the presentinvention include, but are not limited to, spherical, elliptical,quadrilateral, and combinations of these shapes. Alternatively, flow ofthe fluid can be induced using magnetic stir bars or other known mixersthat produce a measuring region suitable for use in the presentinvention. A variety of methods can be employed to induce flow in thefluid consistent with the methods of the present invention. Suitablemethods for platelet-containing fluids will expose the fluid torelatively low shear stresses and minimize and/or avoid damage to fluidcomponents. Alternatively, the rotation can be powered byelectromagnetic force. If the rotor is driven electromagnetically, amagnetic stir bar could be used or a bar made of magnetic material suchas iron would be embedded within the rotor.

In FIG. 3, several non-limiting examples of various disruption membershaving a variety of shapes and contours are shown. Each of thedisruption members 14 shown, as well as others, can include simplestraight rods, magnetic stir bars, baffles, more complex fin-likedesigns, unattached vagile objects, or other means for mixing the fluid.

In an alternative embodiment of the present invention, flow of the fluidcan also be induced using forced flow. FIGS. 4A and 4B illustrate forcedflow configurations in accordance with principles of the presentinvention. Specifically, two similar embodiments, illustrated generallyat 40 a and 40 b, respectively, show two mixing regions 34 a and 34 bconnected by an elongated streamline flow path or measuring region 36.The fluid is forced from mixing region 34 a toward mixing region 34 bvia flow path 36 using pistons 30 a and 30 b. As piston 30 a movestoward the flow path 36, fluid is mixed in mixing region 34 a, and isfurther mixed as the fluid exits the measuring region 36 and entersmixing region 34 b. During this movement, piston 30 b moves away fromthe measuring region 36 to increase the volume of mixing region 34 b.Following the completion of this forced flow in one direction theprocess is reversed by moving piston 30 b toward the measuring region 36and forcing the fluid back to the left along measuring region 36. Thoughtwo pistons are shown and described, the presence of two pistons is notrequired. This effectuates mixing in each of the mixing regions 34 a and34 b. The measuring region 36 provides streamlined flow suitable for usein the present invention using measurement device 32, as in previouslydescribed embodiments. In this embodiment of the present invention, theflow recirculates through the apparatus in a bi-directional manner, e.g.the fluid in the measuring region traverses the same path in alternatingflow directions.

In addition to that described above, the mixing regions can take variousshapes and dimensions consistent with the methods of the presentinvention. For example, a region of narrowing geometry in the mixingregion, where the mixing region begins to narrow toward the measuringregion 36, is an area of vortex formation. There, sufficient mixing canoccur to facilitate aggregation and homogenization of the fluid. Theregion of converging geometry is also an area where there aresignificant inter-platelet collisions, which also aids aggregation andaccurate measurement. Stir bars 38 a, 38 b can also be incorporated inthe narrowing areas of the reservoirs to further enhance mixing ifdesired, as shown in FIG. 4A. The elongated measuring region 36 is aregion where there is streamlined flow that facilitates detection ofaggregation or other fluid properties, especially by light scattering asdiscussed above. The elongated measuring region 36 can be made ofmaterials similar to that of the mixing regions 26 a and 26 b.Preferably, at least a part of the conduit must permit passage ofelectromagnetic signals. If this embodiment were to be used with aLSWBPA, at least a portion of the flow path would be transparent tolight. The interface between the piston and the wall of the mixingregions will generally form a seal and be substantially impermeable tothe fluid.

In another aspect of the present invention, streamlined flow can beinduced in a fluid by an external drive, such as by rotating the fluidcontainer while holding a rotor stationary (or rotating at a differentrate or direction), or by otherwise moving the fluid container to causefluid flow having the above described characteristics of a mixing and ameasuring region within the container.

In yet another aspect of the present invention consistent with the abovedescription, FIG. 5A shows a fluid property measurement system 50. Afluid container 52 can include a fluid movement device such as a rotor54 positioned within the fluid container. The fluid movement device canbe configured to produce flow of fluid within the container along adesired fluid flow path, e.g., causing circumferential recirculation. Inthe case of FIG. 5A, the fluid flow path is an annular recirculatingflow as the rotor spins within the fluid container. A cap 55 can beconfigured to fit over the rotor within the fluid container as shown toprovide a seal and to prevent loss or contamination of the contentsduring use. The fluid container and cap can optionally include threadedsurfaces to allow mating of the two pieces. Alternatively, the cap canbe secured via an interference fitting, latch, snap, adhesive, seal,and/or other similar mechanism.

The measuring region can be a constricted region where fluid flow passesthrough a volume having a smaller cross-sectional area than neighboringvolumes along the fluid flow path. FIG. 5B is a cross-sectional view ofthe system 50 of FIG. 5A having the rotor removed. A constricted region56 can be formed which generates a region of streamlined flow within theconstricted region, shown generally by three flow lines 57. Thus, theconstricted region can cause the fluid to increase in velocity over aportion of the fluid flow path. An increase in fluid velocity canimprove particulate measurement results based on light scattering. Theconstriction can also facilitate fluid dynamic focusing thatconcentrates particulates to be measured in the detection region. Inaddition, increased fluid velocity can reduce agglomeration or blockageof the fluid flow path. Such methods can benefit from increasedresolution and decreased signal-to-noise ratio as fluid flow isincreased. As the fluid exits the constricted region, at least somemixing occurs as the fluid expands outside of the constricted regioninto a mixing region 58. Advantageously, the constricted region andsubsequent expansion that occurs in the mixing region thus acts toprovide streamlined flow and mixing using a single feature, e.g.,stenotic baffle. Such expansion mixing also achieves some of thepurposes of the present invention by reducing damage to platelets andother fragile materials.

The constricted region shown in FIG. 5B is a stenotic baffle systemincluding a top baffle 60, which in this embodiment is positioned on thecap 55 to form an upper streamlined flow surface for the constrictedregion 56. A bottom baffle 64 can also be formed along a lower innersurface 66 of the fluid container to form a lower streamlined flowsurface of the constricted region. In the embodiment shown in FIG. 5B,though the top baffle is positioned on the cap, the top baffle canalternatively be attached to or formed as in integral part of the fluidcontainer. It should be noted that though not necessary, a secondarydisruption member such as those shown and described in connection withFIGS. 1A, 1B, and 3 can also be used in conjunction the stenotic baffleembodiment described herein. The secondary disruption member can bepositioned anywhere except in the constricted region (as it woulddisrupt the streamlined flow), but is preferably positioned at or nearthe mixing region 58 following the streamlined stenotic baffle.

FIG. 5C is a top view of the fluid property measurement system 50 havingthe cap removed. From this perspective, the bottom baffle 64 can be seenhaving a width which covers nearly the entire fluid path width. In oneembodiment, the distance between the rotor and the baffles can becarefully chosen in order prevent damage to fluid which passestherebetween while also maximizing the constricting affect of thestenotic baffle system. Typically, the stenotic baffles system can havea width from about 50% to about 95%, and preferably about 75% to about95% of the shortest distance between the inner wall and the rotor.Further, the bottom baffle can be oriented adjacent a light transparentwindow 68 which is also placed along at least a portion of theconstricted region. The constricted region, or measuring region, canallow the light transparent window to be used for measurement ofaggregation or other particulates via light scattering devices or otherproperty measurement devices as described above. The light transparentwindow can alternatively be translucent, as long as the wavelength oflight used can pass through the window functionally. The constrictedregion can alternatively be formed by using a single stenotic baffle. Inyet another aspect of the present invention, the constricted region canbe formed having conically fluted entrance and exit points. In oneembodiment, the baffle or baffle assembly design can produce threedimensional velocity vectors that result in radial, circumferential,and/or vertical mixing.

In each of the embodiments described above, the fluid container includesa region(s) where the local flow patterns of the fluid are such thatthere is substantial mixing of the fluid. Further, the fluid containerincludes another region(s) separate from the mixing region(s) where theflow characteristics are substantially streamlined. Such streamlinedflow is steady enough that the entities of interest in the fluid, e.g.platelet aggregates in a blood component-containing fluid, carried in itcan be detected more accurately by certain detection methods, such aslight scattering. As recirculation occurs in the measuring region, amore complete sample of fluid can also be measured. Moreover, the abovemixing and streamlined flow characteristics are induced using methodsthat minimize damage to, or alteration of entities of interest, e.g.,platelet aggregates and coagulated masses. In addition, the presentinvention can be incorporated into a compact, disposable, and ergonomicdesign that further enables more reliable assessments of plateletfunction.

Further, the systems and devices of the present invention are designedto measure of free stream particulates such as platelet aggregates. Thefluid flow velocity, disruption member designs such as constrictedregions or baffles, and other variables can be adjusted to encourageaggregation of platelets while in the fluid rather than impact andagglomeration on an interior surface of the device. For example, arelatively high shear rate, e.g. 200 s⁻¹ to 2000 s⁻¹ can be maintainedin order to prevent platelet aggregates from adhering to walls orbaffles. Thus, in one embodiment, the systems of the present inventioncan measure free stream aggregation with significantly reduced concernsand affects associated with clogging and blockage which can occur asmasses of material build up on moving parts or other surfaces.

EXAMPLES

The following examples illustrate embodiments of the invention that arepresently known. Thus, these examples should not be considered aslimitations of the present invention, but are merely in place to teachhow to make the best-known systems and methods of the present inventionbased upon current experimental data. As such, a representative numberof systems and methods are disclosed herein.

Example 1

A cylindrically shaped fluid container having an inner diameter of 11mm, a height of 20 mm, and a wall thickness of 2 mm was obtained. Thefluid container is formed of a polycarbonate, coated on the innersurface with a non-tacky coating to increase compatibility with blood. Acylindrical cap, having an 11 mm inner diameter and 20 mm height made ofthe material DELRIN™ was fitted to substantially seal the inner diameterof the fluid container. The cap had a 4 mm diameter hole in the center,extending entirely through the height of the cap, i.e., 20 mm, andincludes a side notch measuring 5 mm by 5 mm (also extending the entirelength of the cap). The rotor included a cylindrical shaft 24 mm inlength and 4 mm in diameter, and a rotor body that was 6 mm in diameterand 6 mm in length. The bottom of the rotor body included a sharppointed tip with a 30° angle similar to rotor 20 a shown in FIG. 1A. Adisruption member was present that included a cylindrical protrusionmeasuring 3 mm in diameter and 2 mm in length, which was molded as partof the interior of the container wall. The disruption member waspositioned 3 mm from the bottom of the side wall and had a cylindricalaxis oriented along the radial direction of the container. This cylinderhad a 45° bevel cut on the side facing the center of the container.

The apparatus was then used to measure platelet aggregation of wholeblood as follows: Blood (0.2 ml) was injected into the fluid container.A rotational speed of about 600 RPM was set for the rotor. Adifferential light-scattering detector was positioned externally on aside opposite the disruption member. A blood baseline was measured withthe detector for a period of 5 seconds to set the platelet aggregatethreshold. After the measurement of the baseline and the establishmentof the threshold, a platelet-aggregating agent of 10 μl ADP solution wasinjected into the moving blood resulting in a final concentration of ADPin blood of 50 μM. Platelet aggregates formed under the stimulation ofthe ADP and the flow and mixing induced by the rotor and disruptingmember. In regions opposite the mixer, i.e., the streamlined flow ormeasuring region, where the detector was located, the blood flow isessentially streamline. Hence, the detector measured the plateletaggregates that were entrained inside the blood flow as distinctivespiked signals above or below the baseline. As these signals developedbeyond the threshold, they were recorded. After 2 minutes ofmeasurement, the recording was terminated and the entire fluid containerwith the blood inside was discarded.

Example 2

A fluid container including two identical reservoirs connected by anelongated conduit was formed, similar to the embodiment shown in FIG.4A. The base of each reservoir was 20 mm in diameter and the length ofeach reservoir was 30 mm. At 20 mm below each base, the diametergradually decreased to 3 mm at the top. The reservoirs were made ofpolypropylene, coated with a non-adhesive coating to increase bloodcompatibility. At the base of each reservoir was a piston that was 20 mmin diameter and 10 mm in length. The movement of the piston up and downinto each respective reservoir was propelled by a linear actuator. Thenarrow ends of the reservoirs were connected with a conduit of polyvinylchloride tubing having a 3 mm inner diameter, a 1.5 mm wall thickness,and 40 mm length. One reservoir contained a 2 mm circular injection portand a self-sealing rubber diaphragm 5 mm from the top.

A volume of 1 ml of whole blood was transferred into one of the tworeservoirs prior to attachment of the piston. The piston was thenattached to the base of that reservoir to seal in the blood. The twopistons were moved up and down oppositely in synchrony so that the bloodwas transferred between the two reservoirs through the conduit. Averageflow velocity inside the conduit was 20 mm per second. After theestablishment of the baseline and threshold, a platelet-aggregatingagent was injected into one reservoir through the self-sealing diaphragmport. Under the stimulation of the agent and with the help of the mixingbrought on by the contraction-expansion of blood flow, plateletaggregates formed inside the sample holder. As these platelet aggregateswere carried by the blood through the conduit, they were measured by adetector placed along the conduit and recorded. After 2 minutes ofmeasurement, the recording was stopped, and the whole sample holder wasretrieved for recycling.

Example 3

A cylindrically shaped fluid container having an inner diameter of 10mm, a height of 8 mm, and a wall thickness of 1 mm was obtained. Thefluid container is formed of a polycarbonate, coated on the innersurface with a non-tacky coating to increase compatibility with blood. Acylindrical cap, having a 10 mm inner diameter and 4 mm height made ofthe material DELRAN™ was fitted to substantially seal the inner diameterof the fluid container. The rotor included a cylindrical shaft 24 mm inlength and 4 mm in diameter, and a rotor body that was 6 mm in diameterand 6 mm in length. The bottom of the rotor body included a plug tipwhich fit into a recess in the bottom of the fluid container similar torotor 54 shown in FIG. 5A. A stenotic baffle system was present thatincluded a top baffle having a total length of 7 mm, inclined portionsover 2 mm at a 60° incline, and a flat lower portion having a length of3 mm. A corresponding lower baffle was formed having the same dimensionsas the top baffle. Each stenotic baffle of the assembly was about 3 mmwide at their center and the annular space between the rotor and innerwalls was about 1.5 mm. The stenotic baffles were formed ofpolycarbonate and DELRAN™. A transparent window measuring 3 mm by 3 mmis formed as part of the fluid container wall adjacent the stenoticbaffle system.

The apparatus was then used to measure platelet aggregation of wholeblood as follows: Blood (0.2 ml) was placed into the fluid container. Arotational speed of about 600 RPM was set for the rotor. A differentiallight-scattering detector was positioned externally on a side oppositethe disruption member. A blood baseline was measured with the detectorfor a period of 3 seconds to set the platelet aggregate threshold. Afterthe measurement of the baseline and the establishment of the threshold,a platelet-aggregating agent of 0.2 mM solution was injected into themoving blood resulting in a final concentration of ADP in blood of 10μM. Platelet aggregates formed under the stimulation of the ADP and theflow and mixing induced by the rotor and constricting region. In theconstricting region, the streamlined flow or measuring region, where thedetector was located, the blood flow is essentially streamline. Hence,the detector measured the platelet aggregates that were entrained insidethe blood flow as distinctive spiked signals above or below thebaseline. As these signals developed beyond the threshold, they wererecorded. After 2 minutes of measurement, the recording was terminatedand the entire fluid container with the blood inside was discarded.

The above description and examples are intended only to illustratecertain potential uses of this invention. It will be readily understoodby those skilled in the art that the present invention is susceptible ofa broad utility and applications. Many embodiments and adaptations ofthe present invention other than those herein described, as well as manyvariations, modifications, and equivalent arrangements will be apparentfrom or reasonably suggested by the present invention and the forgoingdescription thereof without departing from the substance for scope ofthe present invention. Accordingly, while the present invention has beendescribed herein in detail in relation to its preferred embodiment, itis to be understood that this disclosure is only illustrative andexemplary of the present invention and is made merely for purpose ofproviding a full and enabling disclosure of the invention. The forgoingdisclosure is not intended or to be construed to limit the presentinvention or otherwise to exclude any such other embodiment,adaptations, variations, modifications and equivalent arrangements, thepresent invention being limited only by the claims appended hereto andthe equivalents thereof.

1. A fluid property measurement system for measuring free streamparticulates, comprising: a) a fluid movement device configured to causebi-directional forced fluid flow within a fluid container along a fluidflow path when a fluid is present in the fluid container; b) aconstricted region along the fluid flow path which subjects the fluidwithin the container to a region of concentrated streamlined flow withinthe constricted region and mixing of the fluid outside of theconstricted region; and c) a property measuring device positioned withrespect to the constricted region to measure fluid properties in theregion of streamlined flow.
 2. The fluid property measurement system asin claim 1, wherein the fluid is present in the system and is selectedfrom the group consisting of blood, platelet suspension, leukocytesuspension, red blood cell suspension, plasma, and combinations thereof.3. The fluid property measurement system as in claim 1, wherein thefluid is present in the system and further comprises a stimulatingagent.
 4. The fluid property measurement system as in claim 3, whereinthe stimulating agent is an aggregating agent.
 5. The fluid propertymeasurement system as in claim 3, wherein the stimulating agent isdispensed into the fluid container after the fluid has been dispensedinto the fluid container.
 6. The fluid property measurement system as inclaim 3, wherein the stimulating agent is dispensed into the fluidcontainer before the fluid has been dispensed into the fluid container.7. The fluid property measurement system as in claim 3, wherein thestimulating agent is combined with the fluid to form a mixture beforethe mixture is introduced into the fluid container.
 8. The fluidproperty measurement system as in claim 3, wherein the stimulating agentand the fluid are introduced simultaneously into the fluid container. 9.The fluid property measurement system as in claim 3, wherein thestimulating agent is selected from the group consisting of gases,liquids, solids, and combinations thereof.
 10. The fluid propertymeasurement system as in claim 1, wherein the fluid is present in thesystem and contains exogenous additives.
 11. The fluid propertymeasurement system as in claim 1, wherein the fluid movement device is apair of plungers positioned at opposing ends of the fluid container. 12.The fluid property measurement system as in claim 1, further comprisinga secondary disruption member which contributes to mixing of the fluid.13. The fluid property measurement system as in claim 12, wherein thesecondary disruption member is an obstruction attached to or on an innersurface of the fluid container.
 14. The fluid property measurementsystem as in claim 1, wherein the property measuring device is based onlight scattering.
 15. The fluid property measurement system as in claim1, wherein the constricted region causes the fluid to increase invelocity over a portion of the fluid flow path.
 16. The fluid propertymeasurement system as in claim 1, wherein the constricted region, whenin operation, causes the fluid to become dynamically focused within theconstricted region.
 17. The fluid property measurement system as inclaim 1, wherein the container is evacuated.
 18. The fluid propertymeasurement system as in claim 1, wherein the constricted region isformed by a stenotic baffle system.
 19. The fluid property measurementsystem as in claim 18, wherein the stenotic baffle system includes a topbaffle along an inner surface of the fluid container or along a cap onthe fluid container to form an upper streamlined flow surface in theconstricted region and a bottom baffle along a lower inner surface ofthe fluid container to form a lower streamlined flow surface in theconstricted region.
 20. The fluid property measurement system as inclaim 1, wherein the constricted region facilitates fluid dynamicfocusing that concentrates particulates to be measured in the region ofconcentrated streamlined flow.
 21. The fluid property measurement systemas in claim 1, wherein the constricted region and fluid movement deviceare configured to provide free stream aggregation of material.
 22. Amethod for measuring properties of a fluid, comprising the steps of: a)placing a quantity of fluid in a container; b) inducing bi-directionalforced flow in the fluid with a fluid movement device, wherein the flowis substantially streamlined in at least a measuring region of thecontainer by constricting flow, and wherein the fluid is recirculatedthrough the measuring region by the bi-directional forced flow; c)creating a mixing region separate from the measuring region of thecontainer sufficient to substantially mix the fluid, said mixing regiongenerated by expanding flow of the fluid from the constricted flow ofthe measuring region; and d) measuring a property of the fluid in themeasuring region.
 23. A method as in claim 22, further comprising thestep of introducing a stimulus to the fluid prior to measuring aproperty of the fluid.
 24. A method as in claim 23, further comprisingthe step of measuring the property of the fluid at an initial time priorto introducing the stimulus.
 25. A method as in claim 23, wherein thestimulus is selected from the group consisting of an aggregating agent,mechanical stimulus, biological stimulus, chemical stimulus, andcombinations thereof.
 26. A method as in claim 22, wherein the steps ofinducing flow and creating a mixing region do not detrimentally alterthe properties of the fluid.
 27. A method as in claim 22, wherein thefluid is selected from the group consisting of blood, plateletsuspension, leukocyte suspension, red blood cell suspension, plasma, andcombinations thereof.
 28. A method as in claim 22, wherein the fluid isa non-physiological fluid.
 29. A method as in claim 22, wherein the stepof inducing flow and creating the mixing region occur under conditionssuch that free stream aggregation of material occurs.
 30. A method as inclaim 22, wherein the step of creating the mixing region is accomplishedby a stenotic baffle system.
 31. A method as in claim 22, wherein stepsa)-d) are performed sequentially.
 32. A method for measuring plateletaggregation, comprising steps of: a) placing a quantity of fluid in acontainer wherein the fluid includes a blood component and anaggregating agent; b) inducing bi-directional forced flow in the fluidwith a fluid movement device positioned in the container, wherein theflow is substantially streamlined in at least a measuring region of thecontainer by constricting flow, and wherein all of the fluid isrecirculated through the measuring region by the bi-directional forcedflow; c) creating a mixing region separate from the measuring regionsufficient to substantially mix the fluid and contribute to free streamaggregation of the blood component, said mixing region generated byexpanding flow of the fluid from the constricted flow of the measuringregion; and d) measuring platelet aggregation of the fluid in themeasuring region using a light scattering device.
 33. A system formeasuring properties of a fluid, comprising: a) a fluid container; b)means positioned with respect to the container for inducingbi-directional forced flow in a fluid present within the container,wherein the flow is substantially streamlined in at least a measuringregion of the container by constricting flow, and wherein the fluid isrecirculated through the measuring region by the bi-directional forcedflow; c) means for creating a mixing region separate from the measuringregion, sufficient to substantially mix the fluid, said mixing regiongenerated by expanding flow of the fluid from the constricted flow ofthe measuring region; and d) a property measuring device operativelyassociated with the measuring region.
 34. A system as in claim 33,wherein the means for creating the mixing region is a stenotic bafflesystem affixed to an inner surface of the container.
 35. A system as inclaim 33, wherein the fluid is selected from the group consisting ofblood, platelet suspension, leukocyte suspension, red blood cellsuspension, plasma, and combinations thereof.
 36. A fluid propertymeasurement system for measuring free stream particulates, comprising:a) a pair of plungers positioned at opposing ends of a fluid containerconfigured to cause bi-directional forced fluid flow within the fluidcontainer along a fluid flow path when a fluid is present in the fluidcontainer; b) a constricted region along the fluid flow path whichsubjects the fluid within the container to a region of concentratedstreamlined flow within the constricted region and mixing of the fluidoutside of the constricted region; and c) a property measuring devicepositioned with respect to the constricted region to measure fluidproperties in the region of streamlined flow.
 37. A fluid propertymeasurement system for measuring free stream particulates, comprising:a) a fluid movement device configured to cause bi-directional forcedfluid flow within a fluid container along a fluid flow path when a fluidis present in the fluid container, wherein the fluid container ispre-evacuated; b) a constricted region along the fluid flow path whichsubjects the fluid within the container to a region of concentratedstreamlined flow within the constricted region and mixing of the fluidoutside of the constricted region; and c) a property measuring devicepositioned with respect to the constricted region to measure fluidproperties in the region of streamlined flow.
 38. A fluid propertymeasurement system for measuring free stream particulates, comprising:a) a fluid movement device configured to cause bi-directional forcedfluid flow within a fluid container along a fluid flow path when a fluidis present in the fluid container; b) a constricted region situatedalong the fluid flow path and formed by a stenotic baffle system thatsubjects the fluid within the container to a region of concentratedstreamlined flow within the constricted region and mixing of the fluidoutside of the constricted region; and c) a property measuring devicepositioned with respect to the constricted region to measure fluidproperties in the region of streamlined flow.
 39. The fluid propertymeasurement system as in claim 38, wherein the stenotic baffle systemincludes a top baffle along an inner surface of the fluid container oralong a cap on the fluid container to form an upper streamlined flowsurface in the constricted region and a bottom baffle along a lowerinner surface of the fluid container to form a lower streamlined flowsurface in the constricted region.
 40. A method for measuring propertiesof a fluid, comprising the steps of: a) placing a quantity of fluid in acontainer; b) inducing bi-directional forced flow in the fluid with afluid movement device, wherein the flow is substantially streamlined inat least a measuring region of the container by constricting flow, andwherein the fluid is recirculated through the measuring region by thebi-directional forced flow; c) creating a mixing region separate fromthe measuring region of the container sufficient to substantially mixthe fluid, said mixing region generated by expanding flow of the fluidfrom the constricted flow of the measuring region, wherein the mixingregion is created with a stenotic baffle system; and d) measuring aproperty of the fluid in the measuring region.
 41. A system formeasuring properties of a fluid, comprising: a) a fluid container; b)means positioned with respect to the container for inducingbi-directional forced flow in a fluid present within the container,wherein the flow is substantially streamlined in at least a measuringregion of the container by constricting flow, and wherein the fluid isrecirculated through the measuring region by the bi-directional forcedflow; c) a stenotic baffle system affixed to an inner surface of thefluid container and configured to create a mixing region separate fromthe measuring region, sufficient to substantially mix the fluid, saidmixing region generated by expanding flow of the fluid from theconstricted flow of the measuring region; and d) a property measuringdevice operatively associated with the measuring region.